Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Guiding function of positron emission tomographycomputed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma

AIM:To explore the role of positron emission tomographycomputed tomography(PET-CT)examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma(OAML).METHODS:The general clinical data,postoperative PET-CT results,treatment regimens,and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected.Among the 21 patients,five patients underwent surgical treatment alone,13 patients underwent surgical treatment combined with radiotherapy,and three patients underwent surgical treatment combined with chemotherapy.RESULTS:The follow-up period ranged from 8 to 79mo,with four cases of recurrence and no deaths.Through PETCT examination,two patients exhibited both local ocular metabolic elevation and systemic metastasis,and one of these patients had cervical lymph node metastasis,while the other had submandibular and parotid gland metastasis.Nine patients showed only local ocular metabolic elevation,while 10 patients had no abnormal metabolic activity locally.CONCLUSION:PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection,aiding in precise disease staging,and facilitating the development of personalized treatment plans,ultimately improving patient prognosis.

Nodular Lymphoid Hyperplasia of the Colon in an Adult Patient after Covid-19 Infection: A Case Report and Literature Review

Nodular lymphoid hyperplasia of the colon (NLHC) is an uncommon pathology in adults. The disease can be asymptomatic and discovered incidentally or symptomatic, which is often manifested by abdominal pain and motility disorders (diarrhea, constipation). The clinical presentation can also be alarming with rectal bleeding and obstructive symptoms that may be misinterpreted as a neoplastic process. In this paper, we report the case of a 58-year-old female patient with a previous history of appendicetomy. She presented with persistent abdominal pain, chronic constipation and black colored stools, following Covid-19 infection. The physical examination was unremarkable. Colonoscopy examination found a bulging, non-ulcerated mass, measuring 3.5 cm in greatest dimension, located at the right colic angle. Thoraco-abdomino-pelvic computed tomography was performed and showed right colonic wall thickening and enhanced nodule formation. Furthermore, metastatic localization was not detected. After a multidisciplinary meeting, a laparotomy with right hemicolectomy was performed. Histopathological examination of the surgical specimen revealed nodular lymphoid hyperplasia with CD20+, CD5−, CD10+ and BCL2−phenotype on immunohistochemistry. Besides, lymphocytes in interfollicular area are CD3+ T cells. Patient outcome was favorable after surgery and no additional treatment was necessary. Nodular lymphoid hyperplasia of the colon is a benign process whose endoscopic appearance can sometimes raise suspicion of malignancy. The diagnosis can only be established by histological evaluation. Immunohistochemistry is also essential to confirm the diagnosis and to rule out low-grade lymphoma. Clinical evolution is often favorable. However, endoscopic follow-up is necessary in all cases.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P<0.01 and I²>50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-positive early-stage GML after bacterial eradication was 75.18%(95%CI:70.45%-79.91%).P-MA indicated the substantial heterogeneity in CR reported across studies(I2=92%;P<0.01).Meta-regression analysis identified statistically significant effect modifiers,including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.CONCLUSION Comprehensive synthesis of available evidence suggests that H.pylori eradication is effective as the sole initial therapy for early-stage GML.Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR,the present study is a relevant to informing clinical practice.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma

BACKGROUND Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue,known as mucosa-associated lymphoid tissue(MALT)lymphoma,is a type of non-Hodgkin’s lymphoma.The prognosis of primary gastric MALT(GML)patients can be affected by many factors.Clinical risk factors,including age,type of therapy,sex,stage and family hematologic malignancy history,also have significant effects on the development of the disease.The available data are mainly focused on epidemiology;in contrast,few studies have investigated the prognostic variables for overall survival(OS)in patients with primary GML.Based on the realities above,we searched a large amount of data on patients diagnosed with primary GML in the Surveillance,Epidemiology and End Results(SEER)database.The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by com-bining prognostic and determinant variables.AIM To create an effective survival nomogram for patients with primary gastric GML.METHODS All data of patients with primary GML from 2004 to 2015 were collected from the SEER database.The primary endpoint was OS.Based on the LASSO and COX regression,we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index(C-index),calibration curve and timedependent receiver operating characteristic(td-ROC)curves.RESULTS A total of 2604 patients diagnosed with primary GML were selected for this study.A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3.The median follow-up of all patients was 71 mo,and the 3-and 5-year OS rates were 87.2%and 79.8%,respectively.Age,sex,race,Ann Arbor stage and radiation were independent risk factors for OS of primary GML(all P<0.05).The C-index values of the nomogram were 0.751(95%CI:0.729-0.773)and 0.718(95%CI:0.680-0.757)in the training and testing cohorts,respectively,showing the good discrimination ability of the nomogram model.Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model.Overall,the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML.CONCLUSION A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML.Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

Mucosa-associated lymphoid tissue lymphoma of the trachea treated with radiotherapy:A case report

BACKGROUND Mucosa-associated lymphoid tissue(MALT)lymphoma originates in the marginal zone of lymphoid tissue.lung is one of the most frequent non-gastrointestinal organs involved,here known as bronchus-associated lymphoid tissue(BALT)lymphoma.BALT lymphoma of unknown etiology,and most patients are asymptomatic.The treatment of BALT lymphoma is controversial.CASE SUMMARY A 55-year-old man admitted to hospital had a three-month history of progressively coughing up yellow sputum,chest stuffiness,and shortness of breath.Fiberoptic bronchoscopy revealed mucosal visible beaded bumps 4 cm from the tracheal carina at 9 o'clock and 3 o'clock,the right main bronchus,and the right upper lobe bronchus.Biopsy specimens showed MALT lymphoma.Computed tomography virtual bronchoscopy(CTVB)showed uneven main bronchial wall thickening and multiple nodular protrusion.BALT lymphoma stage IE was diagnosed after a staging examination.We treated the patient with radiotherapy(RT)alone.A total dose of 30.6 Gy/17 f/25 d was given.The patient had no obvious adverse reactions during RT.The CTVB was repeated after RT and showed that the right side of the trachea was slightly thickened.CTVB was repeated 1.5 mo after RT and again showed that the right side of the trachea was slightly thickened.Annual CTVB showed no signs of recurrence.The patient now has no symptoms.CONCLUSION BALT lymphoma is an uncommon disease and shows good prognosis.The treatment of BALT lymphoma is controversial.In recent years,less invasive diagnostic and therapeutic approaches have been emerging.RT was effective and safe in our case.The use of CTVB could provide a noninvasive,repeatable,and accurate method in diagnosis and follow-up.

Primary rectal mucosa-associated lymphoid tissue lymphoma treated with only endoscopic submucosal dissection:A case report

BACKGROUND Mucosa-associated lymphoid tissue(MALT)lymphoma is a distinct subtype of non-Hodgkin B cell lymphoma that mostly involves the gastrointestinal tract.The stomach is the most commonly affected site whereas colorectal involvement occurs very rarely.Given its rarity,the management and clinical outcome of colorectal MALT lymphoma are not well established yet.CASE SUMMARY From the superficial capillary bed in the lower rectum.Endoscopic ultrasonography showed homogenous hypoechoic lesions in the deep mucosal layer.Endoscopic submucosal dissection(ESD)was done for accurate histologic diagnosis and treatment and both the rectal lesions were completely removed en bloc and subsequently diagnosed as primary rectal MALT lymphoma.Herein,we report a case of primary rectal MALT lymphoma in a 68-year-old woman that was treated by only ESD,and the 12-month follow-up revealed no tumour recurrence.CONCLUSION These results of our case and previous reports suggest that endoscopic resection alone may be a feasible and safe treatment for primary colorectal MALT lymphoma and allows organ preservation.

Laterally spreading tumor-like primary rectal mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Colorectal mucosa-associated lymphoid tissue(MALT)lymphoma is a rare disease,and only a few cases have been reported to date.It has no specific clinical presentations and shows various endoscopic appearances.There is no uniform consensus on its treatment.With the advancement of endoscopic technology,endoscopic treatment has achieved better results in individual case reports of early-stage patients.CASE SUMMARY We report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination,which incidentally found a 25 mm×20 mm,laterally spreading tumor(LST)-like elevated lesion in the rectum.Therefore,he was referred to our hospital for further endoscopic treatment.Complete and curable removal of the tumor was performed by endoscopic submucosal dissection.We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging.And immunopathological staining showed hyperplastic capillaries in the mucosa.Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria,with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm.In addition,immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2.Gene rearrangement results showed positivity for IGH-A,IGH-C,IGK-B,and IGL.Taking all the above findings together,we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomographyexamination showed no other lesions involved. The patient will be followed byperiodic endoscopic observation.CONCLUSIONIn conclusion, we report a case of rectal MALT with an LST-like appearancetreated by endoscopic submucosal dissection. Further studies will be needed toexplore the clinical behavior, endoscopic appearance, and treatment of rectalMALT.

Gastric low-grade mucosal-associated lymphoid tissue-lymphoma: Helicobacter pylori and beyond

The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.

Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma:Recent progress in pathogenesis and management

Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosaassociated lymphoid tissue(MALT)lymphoma is reviewed.In approximately 90%of cases,Helicobacter pylori(H.pylori)infection plays the causative role in the pathogenesis,and H.pylori eradication is nowadays the first-line treatment for this disease,which leads to complete disease remission in 50%-90%of cases.In H.pylori-dependent cases,microbe-generated immune responses,including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules,are considered to induce the development of MALT lymphoma.In H.pylori-independent cases,activation of the nuclear factor-κB pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1,or inactivation of tumor necrosis factor alpha-induced protein 3(A20)are considered to contribute to the lymphomagenesis.Recently,a largescale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H.pylori eradication is excellent.Treatment modalities for patients not responding to H.pylori eradication include a"watch and wait"strategy,radiotherapy,chemotherapy,rituximab immunotherapy,and a combination of these.Because of the indolent behavior of MALT lymphoma,second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient.

The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma

Helicobacter pylori(H.pylori)infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue(MALT).Increasing evidence shows that eradication of H.pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission.The eradication of H.pylori is the standard care for patients with gastric MALT lymphoma.Cytotoxin-associated gene A(CagA)protein,one of the most extensively studied H.pylori virulence factors,is strongly associated with the gastric MALT lymphoma.CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races.After being translocated into B lymphocytes via typeⅣsecretion system,CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and-independent manners and/or some other pathways,and thereby promotes lymphomagenesis.A variety of proteins including p53and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA.Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.

Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma

Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma.Despite its increasing incidence,diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings,and,thus,a high index of suspicion,and multiple,deep,repeated biopsies at abnormally and normally appearing sites in the stomach are needed.In addition,testing for Helicobacter pylori(H.pylori)infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H.pylori eradication and for assessment of disease progression.In addition,H.pylori infection and MALT lymphoma development are associated,and complete regression of low-grade MALT lymphomas after H.pylori eradication has been demonstrated.Radiotherapy and/or chemotherapy can be used in cases that show poor response to H.pylori eradication,negativity for H.pylori infection,or high-grade lymphoma.

Reactive lymphoid hyperplasia of the liver:Perinodular enhancement on contrast-enhanced computed tomography and magnetic resonance imaging

We report the case of a 69-year-old woman with reactive lymphoid hyperplasia(RLH) of the liver.She underwent partial hepatectomy under a preoperative diagnosis of hepatocellular carcinoma; however,histopathological analysis revealed RLH.The liver nodule showed the imaging feature of perinodular enhancement in the arterial dominant phase on contrast-enhanced computed tomography and magnetic resonance imaging,which could be a useful clue for identifying RLH in the liver.Histologically,the perinodular enhancement was compatible with prominent sinusoidal dilatation surrounding the liver nodule.

Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

Mucosa-associated lymphoid tissue(MALT)lymphoma is an indolent extranodal marginal zone B-cell lymphoma,originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus,most notably chronic infection by Helicobacter pylori(H.pylori).This antigenic stimulation initially leads to lymphoid hyperplasia;the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways,with disease progression due to proliferation and resistance to apoptosis,and the emergence of a malignant clone.There are descriptions of MALT lymphomas affecting practically every organ and system,with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors;nevertheless,the digestive system(and predominantly the stomach)is the most frequently involved location,reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens,high mucosal permeability,large extension and intrinsic lymphoid system.While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H.pylori infection,the presence of immortalizing genetic abnormalities,of advanced disease or of eradication-refractoriness requires a more aggressive approach which is,presently,not consensual.The fact that MALT lymphomas are rare neoplasms,with a worldwide incidence of 1-1.5 cases per105population,per year,limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

Pseudolymphoma (reactive lymphoid hyperplasia) of the liver:A clinical challenge

Reactive lymphoid hyperplasia(RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision.

Antitumor immunity by a dendritic cell vaccine encoding secondary lymphoid chemokine and tumor lysate on murine prostate cancer

Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine （SLC） cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC＋lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction （RT-PCR）. The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results： We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC＋lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos- phate buffer solution （PBS） counterparts （P 〈 0.01）. Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4＋, CD8＋ T cell and CD11c＋ DC within established tumor treated by SLC＋lysate-DC vaccine than other DC vaccines （P 〈 0.01）. Conclusion： DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4＋, CD8＋ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma

Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

Innate lymphoid cells(ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs(including natural killer(NK) cells and ILC1 s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs(ILC2 s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin(IL)-5 and IL-13; and, group 3 ILCs(including lymphoid tissue-like cells and ILC3 s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.